1. Technical Field
The present invention relates to compositions and methods for treating inflammation. More specifically, the present invention relates to anti-inflammatory compounds in combination with hydrogen and hydrogen-generating compounds for treating inflammation.
2. Background Art
There are currently many anti-inflammatory/anti-pain agents that are used to treat inflammation and pain in patients. These agents generally include steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Steroids generally act to reduce inflammation by binding to the glucocorticoid receptor, whereas NSAIDS generally act to inhibit both cyclooxygenase-1 (COX-1) and cyclooxygenase (COX-2), thus inhibiting the catalysis of the formation of the inflammation messengers prostaglandins and thromboxane.
These anti-inflammatory/anti-pain agents are widely used but can have many adverse side effects. Steroids have been shown to cause hyperglycemia, insulin resistance, diabetes, osteoporosis, cataracts, anxiety, depression, colitis, hypertension, ictus, erectile dysfunction, hypogonadism, hypothyroidism, amenorrhea, retinopathy, and teratogenic defects. NSAIDS have been shown to cause gastrointestinal adverse reactions (nausea, dyspepsia, gastric ulceration and bleeding, diarrhea), myocardial infarction, stroke, erectile dysfunction, renal adverse reactions (salt and fluid retention, hypertension, interstitial nephritis, nephrotic syndrome, acute renal failure, acute tubular necrosis), photosensitivity, teratogenic defects, premature birth, miscarriage, raised liver enzymes, headache, dizziness, hyperalaemia, confusion, bronchospasm, rashes, swelling, and irritable bowel syndrome.
One particular anti-inflammation and anti-pain agent that has previously been widely used is gabapentin (NEURONTIN®, Pfizer, Inc.). Gabapentin is a GABA analogue and is indicated for controlling seizures as well as for relieving neuropathic pain. Pain relief is brought about with gabapentin by changing the way in which the body senses pain. More specifically, gabapentin prevents excessive electrical activity in the brain by mimicking the activity of the neurotransmitter GABA. GABA is a natural nerve calming agent, and by mimicking this action, gabapentin can calm nerve activity in the brain.
The successor drug developed to gabapentin was pregabalin (LYRICA®, Pfizer, Inc.). Pregabalin is also a GABA analogue, and is the S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid. Pregabalin is indicated for neuropathic pain and seizures, and is more specifically indicated for chronic pain disorders such as fibromyalgia. Pregabalin has been preferred over gabapentin due to the fact that it can provide the same efficacy but at much lower doses than are required for gabapentin. Equivalent efficacy at a lower dose can be achieved with pregabalin due to the fact that it has a higher bioavailability and is rapidly absorbed by the body in comparison to gabapentin. Therefore, administering pregabalin can overcome some adverse side effects related to dosing with gabapentin. However, adverse effects can still remain when taking pregabalin, such as commonly reported dizziness or drowsiness, as well as withdrawal effects and other effects as described above.
Therefore, there remains a need for an anti-inflammatory/anti-pain agent that is effective in treating inflammation and pain but reduces the risk of the above adverse reactions.